ArticleThe Journal of investigative dermatology2014
Fas/Fas ligand mediates keratinocyte death in sunitinib-induced hand-foot skin reaction.
Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Transforming a Roadblock into a Roadmap: Evolving HFSR Management From Adverse Event to Efficacy Biomarker.Current treatment options in oncology · 2026Review
- A review of the immunogenetics of Stevens-Johnson syndrome and toxic epidermal necrolysis.Global medical genetics · 2025Review
- Identification of Keratinocyte Cytoprotectants against Toxicity by the Multikinase Inhibitor Sorafenib Using Drug Repositioning.JID innovations : skin science from molecules to population health · 2024Article
- A Potential Association of Zinc Deficiency and Tyrosine Kinase Inhibitor-Induced Hand-Foot Skin Reaction.Biological trace element research · 2023Review
- Review
- Decoy receptor 3 is involved in epidermal keratinocyte commitment to terminal differentiation via EGFR and PKC activation.Experimental & molecular medicine · 2022Article
- Phase I Study Evaluating Dose De-escalation of Sorafenib with Metformin and Atorvastatin in Hepatocellular Carcinoma (SMASH).The oncologist · 2022Article
- Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy.Cancer cell international · 2019Review
- Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies.Cancer management and research · 2018Review
- Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies.Journal of immunology research · 2018Review
- Oestrogen enhances cardiotoxicity induced by Sunitinib by regulation of drug transport and metabolism.Cardiovascular research · 2015Article
- Fractioned dose regimen of sunitinib for patients with gastrointestinal stromal tumor: a pharmacokinetic and treatment efficacy study.Translational oncology · 2014Article
- Genomic Analysis as the First Step toward Personalized Treatment in Renal Cell Carcinoma.Frontiers in oncology · 2014Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sunitinib, a multitargeted receptor Y kinase inhibitor (TKI) used for the treatment of renal cell carcinoma and gastrointestinal stromal tumor (GIST), is notorious for cutaneous adverse effects, such as hand-foot skin reaction (HFSR). To explore the underlying mechanism of HFSR, we enrolled 53 sunitinib-treated GIST patients, including 23 HFSR cases, and 30 tolerant controls. Among the 29 biomarkers examined, soluble FasL (sFasL) showed significant increase in the plasma, blister fluids, and skin lesions of HFSR patients. The plasma levels of sFasL were significantly correlated with those of sunitinib in HFSR patients. In addition to FasL, augmented expression of Fas and active caspase 3 was also detected in the epidermis of HFSR patients. The increased FasL caused keratinocyte death, as the use of anti-FasL antibody specifically blocked cell apoptosis. Oral administration of sunitinib to mice increased skin susceptibility to mechanical injuries in a dose/time-dependent manner. The administration of sunitinib (40 mg kg(-1) per day) for 4 weeks to mice caused the maximally affected skin area with an erosion-to-ulceration response to tape-stripping. The skin biopsies of mice administered sunitinib exhibited increased expression of Fas and FasL in the apoptotic keratinocytes in the epidermis. Our data revealed that Fas/FasL interaction mediates keratinocyte death in sunitinib-induced HFSR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.